Type 5 17β-hydroxysteroid dehydrogenase (AKR1C3) contributes to testosterone production in the adrenal reticularis

Yasuhiro Nakamura, Peter J Hornsby, Peter Casson, Ryo Morimoto, Fumitoshi Satoh, Yewei Xing, Michael R. Kennedy, Hironobu Sasano, William E. Rainey

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Context: The human adrenal gland produces small amounts of testosterone that are increased under pathological conditions. However, the mechanisms through which the adrenal gland produces testosterone are poorly defined. Objective: Our objective was to define the role of type 5 17β- hydroxysteroid dehydrogenase (AKR1C3) in human adrenal production of testosterone. Design and Methods: Adrenal vein sampling was used to confirm ACTH stimulation of adrenal testosterone production. Adrenal expression of AKR1C3 was studied using microarray, quantitative real-time RT-PCR, and immunohistochemical analyses. AKR1C3 knockdown was accomplished in cultured adrenal cells (H295R) using small interfering RNA, followed by measurement of testosterone production. Results: Acute ACTH administration significantly increased adrenal vein testosterone levels. Examination of the enzymes required for the conversion of androstenedione to testosterone using microarray analysis, quantitative real-time RT-PCR, and immunohistochemistry demonstrated that AKR1C3 was present in the adrenal gland and predominantly expressed in the zona reticularis. Decreasing adrenal cell expression of AKR1C3 mRNA and protein inhibited testosterone production in the H295R adrenal cell line. Conclusions: The human adrenal gland directly secretes small, but significant, amounts of testosterone that increases in diseases of androgen excess. AKR1C3 is expressed in the human adrenal gland, with higher levels in the zona reticularis than in the zona fasciculata. AKR1C3, through its ability to convert androstenedione to testosterone, is likely responsible for adrenal testosterone production.

Original languageEnglish (US)
Pages (from-to)2192-2198
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume94
Issue number6
DOIs
StatePublished - Jun 2009

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Zona Reticularis
Testosterone
Adrenal Glands
Androstenedione
Microarrays
Adrenocorticotropic Hormone
Real-Time Polymerase Chain Reaction
Veins
3(17)-hydroxysteroid dehydrogenase
Zona Fasciculata
Microarray Analysis
Small Interfering RNA
Androgens
Cultured Cells

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

Cite this

Type 5 17β-hydroxysteroid dehydrogenase (AKR1C3) contributes to testosterone production in the adrenal reticularis. / Nakamura, Yasuhiro; Hornsby, Peter J; Casson, Peter; Morimoto, Ryo; Satoh, Fumitoshi; Xing, Yewei; Kennedy, Michael R.; Sasano, Hironobu; Rainey, William E.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 94, No. 6, 06.2009, p. 2192-2198.

Research output: Contribution to journalArticle

Nakamura, Y, Hornsby, PJ, Casson, P, Morimoto, R, Satoh, F, Xing, Y, Kennedy, MR, Sasano, H & Rainey, WE 2009, 'Type 5 17β-hydroxysteroid dehydrogenase (AKR1C3) contributes to testosterone production in the adrenal reticularis', Journal of Clinical Endocrinology and Metabolism, vol. 94, no. 6, pp. 2192-2198. https://doi.org/10.1210/jc.2008-2374
Nakamura, Yasuhiro ; Hornsby, Peter J ; Casson, Peter ; Morimoto, Ryo ; Satoh, Fumitoshi ; Xing, Yewei ; Kennedy, Michael R. ; Sasano, Hironobu ; Rainey, William E. / Type 5 17β-hydroxysteroid dehydrogenase (AKR1C3) contributes to testosterone production in the adrenal reticularis. In: Journal of Clinical Endocrinology and Metabolism. 2009 ; Vol. 94, No. 6. pp. 2192-2198.
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AU - Satoh, Fumitoshi

AU - Xing, Yewei

AU - Kennedy, Michael R.

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